Vitamin C Composition for Use in the Prevention and Treatment of Stretch Marks, Radiation Dermatitis, and Other Skin Conditions and Methods of Using the Same

ABSTRACT

A formulation for a stable ascorbic acid composition which, in a simplified form, is comprised of ascorbic acid in solution with a hygroscopic compound (i.e., a substance with the ability to attract water molecules from the surrounding environment through either absorption or adsorption). Also disclosed herein are methods for the production of such compounds and methods of using such compounds in the prevention, inhibition and treatment of striae gravidarum, radiation dermatitis, rhytids, lentigoes, dyschromia, sun-damage induced hyperpigmentation, cellulite, scars and purpura, among other skin diseases or conditions.

CROSS REFERENCE TO RELATED APPLICATION(S)

This application is a Divisional of U.S. Utility patent application Ser.No. 12/985,098, filed Jan. 5, 2011, which in turn claims the benefit ofU.S. Provisional Patent Application Ser. No. 61/292,365, filed Jan. 5,2010. The entire disclosure of all these documents is hereinincorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This disclosure relates to the field of vitamin C, or ascorbic acid,compositions. This disclosure also relates to the field of treatmentsfor striae, including but not exclusive to, striae gravidarum, striaeatrophicae, striae distensae, and pubertal striae; i.e., stretch marks,and the fields of treatments for radiation dermatitis, rhytids,lentigoes, dyschromia, sun-damage hyperpigmentation, cellulite, purpuraand scars, amongst other skin diseases and conditions.

2. Description of Related Art

Vitamin C, or ascorbic acid, is a water-soluble micronutrient; it is anessential nutrient for humans. The vital role of ascorbic acid in humanphysiology flows from the essential role that ascorbate (an ion ofascorbic acid) plays in a wide range of metabolic reactions. As a strongelectron donor or reducing agent, vitamin C sequentially donates twoelectrons from the double bond between carbons two and three. With theloss of these electrons, vitamin C is oxidized and another compound isreduced. Accordingly, vitamin C is commonly known as an antioxidant.

In humans, vitamin C is an essential cofactor for eight (8) differentenzymes. Three (3) of these enzymes participate in collagenhydroxylation. Collagen is a group of naturally occurring proteins whichare found in the fibrous tissues of the human body such as tendons,ligaments and skin. Ascorbic acid has been found to be an essentialcofactor in the hydroxylation of proline and lysine to formhydroxyproline and hydroxylysine, amino acids necessary for the functionof collagen. In fact, some studies have demonstrated that ascorbic acidcan stimulate collagen synthesis preferentially without affectingnon-collagen protein synthesis. See Murad S., et al., Regulation ofCollagen Synthesis by Ascorbic Acid, Proc. Natl. Acad. Sci., 78:2870(1981).

The same properties that make vitamin C an excellent antioxidant (itselectron donor propensities) render it difficult to create a stablevitamin C formulation, as it generally rapidly oxidizes upon exposure toair. Notoriously, in the presence of water, light, air and/or hightemperatures, vitamin C is not stable, generally having a half life ofminutes. In fact, at higher pHs ascorbic acid increasingly becomes moreunstable. Thus, historically, it has been difficult to develop stablevitamin C compositions. While stabilized topical vitamin C compositionsare known; e.g., See Kaplan, et al., A New Stabilized Ascorbic AcidSolution: Percutaneous Absorption and Effect on Relative CollagenSynthesis, Journal of Cutaneous Aging & Cosmetic Dermatology, 1:115(1988/89) (disclosing a 5% solution of L-ascorbic acid in ahydroalcoholic vehicle), the stability of such compositions generallyhave been shown only up to about one (1) month. After that time, theformulation begins to rapidly oxidize and decompose. Thus, even the“stable” topical vitamin C formulations that are currently known tothose of skill in the art have a minimal shelf life and efficacy period.Furthermore, typically, when these known ascorbic acid solutions areexposed to heat, rapid degradation of the ascorbic acid solutionresults. This instability and potential for rapid degradation of theprior topical vitamin C formulations generally results in a high cost ofmanufacturing, high cost of distribution, and issues associated withstorage and availability to the end consumer.

In addition to issues of stability, there also has been uncertainty withregard to the ability of the currently utilized ascorbic acidcompositions to deliver pharmacologic doses of ascorbic acidpercutaneously (i.e., through the skin) If ascorbic acid is to effectthe connective tissue of the skin, it must penetrate the stratum corneum(i.e., the outermost layer of the epidermis of the skin) and beavailable to the dermal fibroblasts (i.e., the cells of the skin thatsynthesize collagen). While penetration of the stratum corneum withtopical vitamin C solutions for delivery to the dermis (i.e., the layerof skin between the epidermis and subcutaneous tissues) are known, thesesolutions either suffer from a low absorption rate over time (SeeKaplan, et al., A New Stabilized Ascorbic Acid Solution: PercutaneousAbsorption and Effect on Relative Collagen Synthesis, Journal ofCutaneous Aging & Cosmetic Dermatology, 1:115 (1988/89) (Absorptionprogressed linearly for 72 hours and with 12.4% absorption traversingthe epidermal barrier)) or instability of the topical solution itself(See Pinnell, S. R., et al., Topical L-Ascorbic Acid: PercutaneousAbsorption Studies, Dermatol. Surg., 27(2): 137-42 (2001) (showing thatdaily application of an L-ascorbic acid topical solution, with a pH of3.5 or lower, resulted in saturating skin concentrations of L-ascorbicacid at more than 20 times the control values, for four days)).

This difficulty in the art with regard to the ability to deliverpharmacologic doses of ascorbic acid percutaneously has resulted inascorbic acid formulations with four main problems. First, theseformulations often lack a sufficient concentration of ascorbic acid tobe effective. In order to achieve some minimal level of stability, theseformulations have low concentrations of ascorbic acid. Second, theseformulations are often in suspension rather than solution, making theformulation unavailable for percutaneous absorption since it is not in adissolved state. Third, these formulations often incorporate ascorbicacid salts that, while being more stable, do not have the samepharmacological effect as ascorbic acid on the fibroblast for collagensynthesis and do not have the same percutaneous absorptioncharacteristics. Fourth, the rapid degradation of the ascorbic acidprevents the ascorbic acid from reaching its target in the dermal layerof the skin in a stabilized form. Thus, it is unable to exert aphysiologic effect on the fibroblasts.

A stable ascorbic acid composition which could be absorbedpercutaneously would have application in a number of skin diseases andconditions which are associated with a decrease or disruption incollagen synthesis. Striae gravidarum is one such condition. Striaegravidarum, otherwise known as stretch marks, is a commonly known, butpoorly understood, skin disconfiguring condition. Generally, stretchmarks are characterized by a thinning of the connective tissue seroniato produce linear, atrophic-appearing skin. Stretch marks are a commonlyrecognized condition in both adolescent growth and pregnancy, amongother situations.

Although the prevalence of stretch marks is high (among pregnant womenit is reported to range between 50% and 90%) little is known about theaetiology and epidemiology of stretch marks. See Chang, Anne Lynn S,M.D., Risk Factors Associated with Striae Gravidarum, J. Am. Acad.Dermatol., December 2004, page 881. While the development of stretchmarks is commonly thought to be caused by rapid weight gain, excessiveendocrine activity, growth associated with adolescence or a degree ofstretch in pregnancy, there are no scientific studies that verify any ofthese relationships. See Chang, Anne Lynn S, M.D., Risk FactorsAssociated with Striae Gravidarum, J. Am. Acad. Dermatol., December2004, page 881. Further, other preliminary studies have suggested thatfamily history, personal history, and race; i.e., genetic based factors,appear predictive of the development of striae gravidarum. See Chang,Anne Lynn S, M.D., Risk Factors Associated with Striae Gravidarum, J.Am. Acad. Dermatol., December 2004, page 883. While genetic factors,pregnancy weight gain, the growth and hormonal changes associated withadolescence and excessive adrencortical activity are the most frequentcausative factors of stretch marks, the exact aetiology is not known.

In addition to the general confusion surrounding the aetiology andepidemiology of stretch marks, dissimilar descriptions of thehistological changes in striae have created confusion to those of skillin the art. Some studies hypothesize (but have yet to observe) thatstriae are formed by an inflammatory reaction in a very early stage instriae formation that causes destruction of collagen and elastin. As inany other damage, this inflammation is followed by regeneration of newcollagen and elastin, this time oriented in the direction of stressimposed by mechanical forces, as in rapid weight gain. See Zheng, P., etal., Anatomy of Straie, British Journal of Dermatology, 112, 185-193(1985). The resultant damage has been shown, in some studies, tocomprise variously a thin, flattened epidermis, thinning of the dermis,fraying and separation of collagen bundles with dilatation of bloodvessels, and/or separation or total absence of elastic fibers. See Lee,K. S., Decreased Expression of Collagen and Fibronectin Genes in StraieDistensae Tissue, Clinical and Experimental Dermatology, 19:285-288(1994).

Notably, despite its prevalence among pregnant women and adolescents,few preventative treatments are available for stretch marks. While thereare a number of creams on the market that claim to remove stretch marksonce they have developed, there is no reliable evidence to support suchclaims. Similarly, there are only two published randomized trials ofpreventive topical treatments and only one of these used a placebocontrol. From these studies it is not clear which, if any, particularingredient is helpful in the prevention and/or treatment of stretchmarks.

Taken together, the science surrounding the cause and treatment ofstretch marks is in a state of bewilderment. Accordingly, there is aneed in the art for an effective topical composition for the preventionand/or treatment of striae gravidarum, especially since currently thereare no commercially available proven preventive products for stretchmarks.

Radiation dermatitis is another skin condition which is associated witha decrease or disruption in collagen synthesis. Radiation dermatitis(also known as radiodermatitis) is an unintended skin reaction commonlyexperienced by patients receiving radiation therapy as part of theircancer treatment. This side effect, caused by radiation passing throughthe cells, is an unpleasant and painful condition for many cancerpatients which, in some cases, may become so severe as to necessitatethe interruption or cessation of radiation therapy. This, in turn, hasbeen shown to decrease the efficacy of the radiation treatment andincrease the likelihood of a cancer relapse.

Generally, radiation dermatitis manifests within a few weeks after thestart of the radiotherapy. The onset of the condition varies inaccordance with the radiation dose intensity, anatomic location of theradiation therapy, and the normal tissue sensitivity of individuals.This condition is experienced, to various degrees, by the majority ofpatients undergoing radiotherapy. While in most patients the dermatitisis mild to moderate, about 20-25% of patients experience severereactions. Reddening of the skin, known as erythema, is an initial signof skin dermatitis and may appear as early as the first treatment. Othersymptoms also may include: epilation (i.e., hair loss), dry and wetdesquamation (i.e., the shedding of the outer layers of the skin),decreased sweating, edema (i.e., swelling), ulcerations, bleeding, andskin cell death. Generally, the symptom progression has been shown to belinked with the total radiation dose, the dose per fraction, the overalltreatment time, beam type and energy, and the surface area of the skinthat is exposed to radiation. When the skin reaction is severe enough,it can interfere with the scheduling of the treatment regimen, which canadversely affect treatment outcomes by resulting in increased relapsesof the malignancy and decreased patient survival rates.

Despite the prevalence of radiation dermatitis among individualsreceiving radiation treatment, similar to striae gravidarum, there arefew proven or known treatment options. While a variety of lotions,creams, and ointments have been recommended in the literature, there isa paucity of randomized trials with evidence to support the efficacy ofthese treatments. In fact, several trials evaluating topical agents haveraised the question as to whether any product will actually prevent orpromote the healing of radiation skin reactions. M. McQuestion,Evidence-Based Skin Care Management in Radiation Therapy, Seminars inOncology Nursing, Vol 22, No. 3: 163-173 (2006).

Another skin condition associated with a disruption in collagensynthesis is the appearance of rhytids, commonly known as wrinklesWrinkles are grooves in the skin. Wrinkles form when the skin looses itsstrength and elasticity, or the ability to stretch as the person ages. Anumber of factors are thought to be the cause of wrinkles, including:loss of the strength and elasticity of the skin with age; sun damage;repeated facial movements; and the natural effects of gravity, amongothers. Generally, individuals with the highest risk of developingwrinkles are fair-skinned people, people who have increased sun exposureand people who have a genetic predisposition to the development ofwrinkles.

Currently, there is a wide variety of modalities known to those of skillin the art that are employed to treat rhytids. These include, but arenot limited too, injectable fillers, injection of Clostridium Bitulinum(Botox®) or similar bacteria, implants, lifts, chemical peels,dermabrasion, laser resurfacing and/or the application of retinoic acid.These known and utilized treatments can be expensive and/or invasiveoptions for the treatment/reduction of rhytids.

Lentigo, dyschromia (i.e., alteration in color to the skin or hair) andsun-damaged induced hyperpigmentation are additional skin conditionsassociated with disruptions in the production of collagen. Lentigo is abenign hyperplasia of melanocytes which spreads linearly. It generallyshows up as a brown to black pigmented spot on the skin. Generally, theappearance of lentigos depends on varying factors such as anindividual's history of sunlight exposure and genetic predisposition,amongst others. Similar to a lentigo, hyperpigmentation is the darkeningof an area of the skin or nails caused by an increase in melanin.Hyperpigmentation may be caused by sun damage, inflammation, or otherskin injuries. It is associated with a number of diseases, including,but not limited to, Addison's disease, Cushing's disease, and Celiacdisease, amongst other diseases and conditions.

The appearance of cellulite is another skin condition associated withcollagen synthesis. Cellulite is a topographical skin change whichpresents itself as a modification of the topography of the skin,generally evidenced by skin dimpling and nodularity. It occurs in manywomen (mainly in the pelvic region, lower limbs and abdomen) and isgenerally caused by the herniation of subcutaneous fat within fibrousconnective tissue. Cellulite is not a serious medical condition, butmany, for aesthetic reasons, are interested in treatment options for theprevention or reduction of its appearance. While numerous therapies forthe treatment of cellulite are available on both a prescription and anon-prescription basis, the empirical evidence for the efficacy of thesetechniques is limited and questionable.

Sun induced or actinic purpura is also associated with disruptions incollagen synthesis. Purpura, which is caused by bleeding underneath theskin, manifests itself as the appearance of red or purple discolorationson the skin that do not blanch with the application of pressure to theskin. Purpura associated with sun damage are the result of chronic sunexposure which produces damage to the capillaries found in the skin,resulting in easy bruising.

SUMMARY OF THE INVENTION

Due to these and other problems in the art, disclosed herein, amongother things, is a formulation for a stable ascorbic acid composition.This composition, in a simplified form, is comprised of ascorbic acid insolution with a hygroscopic compound (i.e., a substance with the abilityto attract water molecules from the surrounding environment througheither absorption or adsorption). Also disclosed herein are methods forthe production of such compounds and methods of using such compounds inthe prevention, inhibition and treatment of striae gravidarum, radiationdermatitis, rhytids, lentigoes, dyschromia, sun-damage inducedhyperpigmentation, cellulite, scars and purpura, among other skindiseases or conditions.

In one embodiment, the composition comprises: ascorbic acid in solutionwith a hygroscopic compound. This hygroscopic compound can be chosenfrom the group consisting of: glycerin, sucrose, sorbitol, dextrose andcorn syrup.

In another embodiment, the ascorbic acid composition will furthercomprise a silicone-based organic polymer. Possible silicone-basedorganic polymers include dimethicone and cylcomethicone.

In still a further embodiment, the composition can further comprisepanthenol, pantothenic acid, tocopherol, propylene glycol and/orethanol.

In one specific embodiment, the ascorbic acid composition comprises:5-20% ascorbic acid; 95-85% hygroscopic compound; 0-3% silicone-basedorganic polymer; 0-5% pantothenic acid; 0-5% tocopherol; 0-30% propyleneglycol; and 0-20% ethanol.

In another embodiment, the composition consists essentially of ascorbicacid in solution with a hygroscopic compound. In yet another embodiment,the composition consists of ascorbic acid in solution with a hygroscopiccompound.

In each of the embodiments of the composition, the composition willremain stable for at least one month or, in another embodiment, for atleast one year.

In addition, in one embodiment, the purity of ascorbic acid in thecomposition will be at least 95% after two years. In another embodimentof the composition, the purity of the ascorbic acid will be at least 95%after four years.

In one embodiment, the composition will be a topical composition.

Also disclosed herein is a composition of matter comprising: about 10%ascorbic acid in solution with about 90% of a 99% pure glycerin; andabout 1% silicone-based organic polymer.

In addition to compositions, also disclosed herein is a method ofproducing a composition of ascorbic acid in solution with a hygroscopiccompound, the method comprising: heating a hygroscopic compound to about40-70° C.; and adding ascorbic acid to the heated hygroscopic compoundto form a solution. In some embodiments of this method, the hygroscopiccompound will be heated in a covered container. In other embodiments, anagitating device will be used to mix the composition.

Also disclosed herein is a method of stimulating collagen synthesiscomprising: forming a composition of ascorbic acid in solution with ahygroscopic compound; and applying said composition topically to apatient's skin.

In some embodiments of this method, the composition will be topicallyapplied to the patient for the treatment of a skin condition chosen fromthe group consisting of: striae gravidarum, radiation dermatitis,rhytids, lentigoes, dyschromia, sun-damage induced hyperpigmentation,cellulite, scars and pupura.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a chart of the raw materials of an embodiment of thedisclosed topical vitamin C composition.

DESCRIPTION OF PREFERRED EMBODIMENT(S)

This disclosure is intended to teach by way of example and not by way oflimitation. The present disclosure focuses on a formulation for a stableascorbic acid composition. This composition, in a simplified form, iscomprised of ascorbic acid in solution with a hygroscopic compound(i.e., a substance with the ability to attract water molecules from thesurrounding environment through either absorption or adsorption). Alsodiscussed herein are methods for the production of such compositions,along with various alternative methods of using such compounds in theprevention, inhibition and treatment of striae gravidarum, radiationdermatitis, rhytids, lentigoes, dyschromia, sun-damage inducedhyperpigmentation, cellulite, scar reduction and purpura, among otherskin diseases.

In one embodiment of the disclosed ascorbic acid composition insolution, the hygroscopic compound comprises: glycerin, sucrose,sorbitol, dextrose, corn syrup and combinations thereof. However, in noway is this group intended to be exhaustive, as this disclosurecontemplates the use of any hygroscopic compound, known now or in thefuture, to those of skill in the art which has the ability to attractwater molecules from the surrounding environment through eitherabsorption or adsorption. Generally, any means for attracting watermolecules from the environment through absorption or absorption in whichascorbic acid can be placed in solution is contemplated in thisdisclosure. In one embodiment, the composition will consist essentiallyof ascorbic acid in solution with a hygroscopic compound such asglycerin, sucrose, sorbitol, dextrose and/or corn syrup. Thiscomposition may potentially be mixed with other compounds which may ormay not provide additional skin benefits. In another embodiment, thecomposition consists of ascorbic acid in solution with a hygroscopiccompound, which is suitable for the stimulation of collagen synthesis.In one embodiment it is contemplated that a glycerin of a high purity,e.g., 99%, will be utilized as the hygroscopic compound in thecomposition.

While the invention is not intended to be limited to any physiologicaleffect of the modality of the stable topical ascorbic acid composition,it is hypothesized that one explanation for the stability of thisascorbic acid composition (compared to other ascorbic acid compositionsutilized in the art) is that the water attraction qualities of thehygroscopic compound base impede the reduction of the ascorbic acidmixed therewith, thereby reducing the volatility of the ascorbic acid.Stated differently, the hygroscopic nature of the glycerin (or otherhygroscopic compound in which the ascorbic acid is in solution) acts topull any water away from the ascorbic acid, thereby allowing it to bestabilized without being degraded.

In more complex embodiments of the disclosed composition, thecomposition is further comprised of a silicone-based organic polymer, inaddition to the ascorbic acid in solution with the hygroscopic compound.Contemplated silicone-based organic polymers include, but are notlimited to, dimethicone and cylcomethicone. However, any silicone-basedorganic polymer known to those of skill in the art is contemplated inthis disclosure. Generally, these silicone-based organic polymers areadded to the composition for the viscoelastic properties (i.e., viscousand elastic characteristics) they impart, which, while not having aneffect on collagen hydroxylation, do have an effect on certainproperties of the topical composition such as smooth application. Thesesilicone-based polymers are also added, in some embodiments, for theirability to increase the aesthetic performance of the formulation.Generally, glycerin alone does not result in a cosmetically elegantformulation. The addition of the silicone polymers changes the rheologicqualities of the formulation to increase the aesthetic pleasure of theformulation, thereby increasing the likelihood of use by a givenindividual. See. Forster, et al., Rheology of siloxane-stabilized waterin silicone emulsions, Int. J. Cosmet. Sci., 19(4): 173-91 (August 1997)(showing use of silicone copolymers in personal care products canimprove the aesthetic performance of formulations). Although sometimesglycerin alone does not result, in some cases, in a cosmetically elegantformulation, compositions comprised of just a hygroscopic compound, likeglycerin, and ascorbic acid are contemplated herein.

In some embodiments, the silicone-based organic polymers will compriseonly a small percentage of the overall composition. An example of thepercentages of composition of one embodiment of the disclosedcomposition, wherein the components are ascorbic acid, glycerin and asilicone-based organic polymer, is as follows: about 10% ascorbic acidin about 90% of a 99% pure glycerin with about 0-1% of a silicone-basedorganic polymer.

In another embodiment, the composition is comprised of additionalingredients besides a silicone-based organic polymer. Contemplatedadditional ingredients include, but are not limited to, panthenol,pantothenic acid, tocopherol and its derivatives, ethanol and propyleneglycol. Generally, the panthenol and propylene glycol are added to thecomposition for their moisturizing properties. Pantothenic acid, i.e.,vitamin B₅, is included because of its position as an essential nutrientrequired to sustain life. Ethanol is included because of its ability toincrease the stability and absorption of the solution, in addition toits ability to improve the cosmetic elegance of the composition.Tocopherol and its derivatives are included in some embodiments of theformulation for generally two reasons. One, their antioxidantproperties. Two, tocopherol and its derivatives are commonly used ascomponents to stabilized formulations that have high potential foroxidative degradation. Accordingly, although not necessary forstabilization of the composition disclosed herein, tocopherol and itsderivatives can be added to the disclosed formulation for theirsupplementary stabilization qualities.

In alternative or further embodiments, supplemental minerals also may beincluded. Suitable minerals may include one or more minerals or mineralsources. Non-limiting examples of minerals include: chloride, sodium,calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese,molybdenum, phosphorus, potassium, and selenium. Suitable forms of anyof the foregoing minerals include soluble mineral salts, slightlysoluble mineral salts, insoluble mineral salts, chelated minerals,mineral complexes, non-reactive minerals such as carbonyl minerals, andreduced minerals, and combinations thereof.

The compositions also may optionally comprise additional vitamincompositions. The vitamins may be fat-soluble or water soluble vitamins.Suitable vitamins include but are not limited to: vitamin A, vitamin E,vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folicacid, pyridoxine, thiamine, and biotin. The form of the vitamin mayinclude salts of the vitamin, derivatives of the vitamin, compoundshaving the same or similar activity of a vitamin, and metabolites of avitamin.

The composition also may comprise at least one excipient. Non-limitingexamples of suitable excipients include: a preservative, a stabilizer, abinder, a compaction agent, a lubricant, a dispersion enhancer, acoloring agent, and combinations of any of these agents. The excipientalso may comprise a preservative. Suitable examples of preservativesinclude other antioxidants and antimicrobials, such as parabens,chlorobutanol, or phenol.

In an alternative or further embodiment, the excipient may be a binder.Suitable binders include: starches, pregelatinized starches, gelatin,polyvinylpyrolidone, cellulose, methylcellulose, sodiumcarboxymethylcellulose, ethylcellulose, polyacrylamides,polyvinyloxoazolidone, polyvinylalcohols, C₁₂-C₁₈ fatty acid alcohol,polyethylene glycol, polyols, saccharides, oligosaccharides,polypeptides, oligopeptides, and combinations thereof.

In an alternative or further embodiment, the excipient may be alubricant. Suitable non-limiting examples of lubricants include:magnesium stearate, calcium stearate, zinc stearate, hydrogenatedvegetable oils, sterotex, polyoxyethylene monostearate, talc,polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesiumlauryl sulfate, and light mineral oil.

The excipient also may be a dispersion enhancer. Suitable dispersantsmay include: starch, alginic acid, polyvinylpyrrolidones, guar gum,kaolin, bentonite, purified wood cellulose, sodium starch glycolate,isoamorphous silicate, and microcrystalline cellulose as high HLBemulsifier surfactants.

Generally, contemplated ranges for certain components of the compositionin various different embodiments are as follows: about 5-20% ascorbicacid; about 0-3% of a silicone-based organic polymer; about 0-5%pantothenic acid; about 0-5% tocopherol and its derivatives; about 0-20%ethanol; and about 0-30% propylene glycol in about 85-90% hygroscopiccompound. See FIG. 1. In another embodiment of the composition where thecomposition is comprised of ascorbic acid in a hygroscopic compound witha silicone-based organic polymer, contemplated ranges for certaincomponents of the composition are: about 5-20% ascorbic acid in about80-95% hydroscopic compound with about 0-20% silicone-based organicpolymers. Notably, however, in no way is this listing of ranges intendedto be exhaustive, as other ranges could be contemplated in additionalembodiments of the composition.

Generally, the stable topical ascorbic acid composition described hereinmay take any form known to those of skill in the art now or in thefuture for topical solutions including, but not limited to, a solution,a lotion, a shake lotion, a cream, an ointment, a gel, a foam, and/or atransdermal patch. While this application generally discusses the stableascorbic acid solution as a topical composition, alternative methods ofdelivery of compositions are also contemplated. The compositionsdisclosed herein may be formulated into a variety of forms andadministered by a number of different means.

Due, in part, to the rapid oxidation of ascorbic acid upon exposure toheat, air and/or moisture, methods and/or processes for the creation ofascorbic acid compositions have traditionally had low concentrations.For example, according to the Merck Index (i.e., an industry-widerecognized encyclopedia of chemicals, drugs and biologicals), thesolubility of ascorbic acid in glycerol is one (1) gram per one hundred(100) mL of glycerol, a solubility which would result in a finalconcentration of one percent (1%). See Merck Index, Twelfth Addition,Merck & Co., Inc., pp 867-868 (1996). The application of heat and othermethodologies which are generally employed to create a solution withhigher solubility concentrations where traditionally not seen as anoption for the creation of ascorbic acid compositions because of therole heat plays in the oxidation of ascorbic acid.

This traditional limitation in the concentrations of ascorbic acidsolutions is overcome in the processes and methods for the production ofthe stable topical ascorbic acid solutions described herein by thegentle heating of the hygroscopic compound base while the ascorbic acidis added thereto to create a solution. While not intending to be limitedto any particular theory of occurrence, this heating is believed to bepossible because of the water attraction qualities of the hygroscopicbase, which impede the reduction of the ascorbic acid mixed therewith,reducing the volatility of the ascorbic acid. The water attractionproperties of the hygroscopic base not only protect the composition fromdegradation over time caused by exposure to air and moisture, but also,surprisingly, protect the ascorbic acid from degradation upon exposureto heat in certain identifiable ranges.

By this method and process, supersaturated compositions of up to 20%solubility can be achieved without oxidation or degradation of theascorbic acid. As used in this application, degradation means oxidationof the ascorbic acid of the composition to a point at which thecomposition no longer contains a pharmacologically effective quantity ofascorbic acid to stimulate collagen synthesis.

In one embodiment of the method and process, the ascorbic acid is addedto the hygroscopic compound as it is gently heated to a temperaturebetween about 40 to 70 degrees Celcius in a covered container (thecontainer is generally only covered; an airtight vacuum or anoxygen-free seal is not required but can be used in alternateembodiments) using a stirring rod or other mixing or agitating deviceknown to those of skill in the art. Methods and processes for thecreation of ascorbic acid solutions in this manner; i.e., via “gentleheating,” are not known to have been reported in the art. In fact,previous studies and reports in the art teach away from such a method orprocess for the creation of an ascorbic acid solution, as these studiesand reports suggest that ascorbic acid will rapidly degrade uponexposure to air and upon heating. However, as noted further above, thehygroscopic properties of the composition (as a result of thehygroscopic base) are believed to protect the ascorbic acid fromoxidizing under conditions that would normally produce degradation inthe ascorbic acid compositions previously known in the art. Further,surprisingly, the hygroscopic properties of the composition (imparted tothe composition by the hygroscopic base) have been shown to protect theascorbic acid from degradation at raised temperatures between about 40to 70 degrees Celsius for a substantial period of time, in some tests upto seven (7) days.

The advantages of the disclosed topical ascorbic acid composition aregenerally three-fold. First, the disclosed composition is exceedinglystable in comparison to currently known ascorbic acid compositions.Preliminary testing has shown the disclosed composition to be stable forat least up to one (1) year, even after the bottle has been exposed toair.

The extreme stability of the disclosed ascorbic acid compositions isdemonstrated in the test results provided in Table 1. Similar todegradation, the terms “stability” or “stable,” as used in thisapplication, are defined in terms of the pharmacologically effectiveamount of ascorbic acid contained in the composition—the composition isnot stable when it no longer contains a therapeutically effective amountof ascorbic acid to be absorbed percutaneously and to stimulate collagenproduction.

To test the stability of the disclosed ascorbic acid compositions, threedifferent compositions were purposefully aged at room temperature forvarying periods of time. The compositions were then tested to determinethe purity of the ascorbic acid in the aged composition; i.e., todetermine the degree to which the ascorbic acid had oxidized over time.

TABLE 1 Age of Amount of Amount of Purity of pH of Ascorbic CompositionAscorbic Acid in Ascorbic Acid in Ascorbic Acid in Acid in AgedComposition When Tested Original Solution Aged Solution Aged SolutionSolution Ascorbic Acid ~12 months 100 mg/mL 97.32 mg/mL 97.32% 1.91 in10% Glycerin Ascorbic Acid ~52 months 100 mg/mL 96.78 mg/mL 96.78% 2.06in 10% Glycerin Ascorbic Acid ~52 months 150 mg/mL 149.84 mg/mL  99.89%2.10 in 15% Glycerin

As seen in Table 1, stability of the solution was maintained (with apurity of ascorbic acid of 96.78% for a 10% solution and 99.89% for a15% solution) even for a composition aged about 52 months (more thanfour years) at room temperature. Again, purity of ascorbic acid at theselevels in compositions aged for such long durations of time are notknown to have been previously reported in the art. Accordingly, thisapplication contemplates ascorbic acid compositions wherein the purityof the ascorbic acid is at least 90%, 95%, 97% or 99% after at leastfour (4) years of storage. This application also contemplates ascorbicacid compositions wherein the purity of the ascorbic acid is at least90%, 95%, 97% or 99% after at least two (2) years of storage.

Second, heating of the disclosed composition of ascorbic acid in asolution of glycerin (or other hydroscopic compound), even when exposedto air, does not result in degradation of the ascorbic acid in thecomposition. In fact, testing has shown that the disclosed compositioncan be “gently heated” at temperatures of about 40 to 70 degrees Celsiusfor up to seven (7) days without degradation of the ascorbic acid. Thisis in stark contrast to the ascorbic acid compositions of the prior art,in which the ascorbic acid would rapidly degrade in the presence of heatand/or air while in solution.

Third, it is commonly understood in the art that ascorbic acidcompositions with a pH of 5 or higher are exceedingly unstable—thehigher the pH of the ascorbic acid composition, the more rapidly it willoxidize. However, previously, topical ascorbic acid compositions with apH of about 2.5 or lower were generally not recognized as possibilitiesbecause previously known topical ascorbic acid compositions with pHs atthese levels resulted in skin irritation issues and were not toleratedtopically. The disclosed ascorbic acid composition solves both of theseproblems. The hygroscopic base of the disclosed composition, in additionto protecting the ascorbic acid from heat and air associateddegradation, is also a unique solvent because it allows for a lower pH.As demonstrated in Table 1, the pH of the disclosed composition is about2.5 or lower or about 2.0 or lower across a variety of agedcompositions. This lower pH is important because stability is directlycorrelated with the pH of ascorbic acid compositions; the lower the pH,the more stable the composition. Further, even though it has a lower pH,the disclosed composition does not cause skin irritation when appliedtopically.

One contemplated use for the stable topical ascorbic acid compositionsdisclosed herein is for the prevention, inhibition, and/or treatment ofstriae gravidarum. Without any intention to be limited by any theory ormechanism of operation, the hypotheses in the art as to the histologicalchanges in striae support one of the working theories of the presentapplication; i.e., that the mechanical forces on the skin duringpregnancy and puberty (among other conditions commonly associated withthe appearance of striae) result in the clinical changes referred to as“stretch marks,” and that a stabilized formulation of ascorbic acid, ifproperly formulated, would be able to have a pharmacologic effect on thefibroblasts, augmenting the production of normal collagen and elastin ofsufficient quantity and quality to prevent formation of stretch marksand/or reduce the appearance of stretch marks. Ascorbic acid could alsopossibly contribute an anti-inflammatory effect, as well as ananti-oxidative effect, on the fibroblasts.

In one embodiment of a method of using the stable topical ascorbic acidcomposition disclosed herein for the prevention of striae gravidarum,the topical ascorbic acid composition is applied to the body surfaces ofa pregnant woman that are common sites for the appearance of striaegravidarum; e.g., breasts, hips, thighs, and abdomen. Frequency of theapplication can vary, from several applications a day to once every fewdays, to once every week. Similarly, the duration of the application canvary from a quick application until absorbed into the skin to a longerapplication associated with massage of the treated skin area. Further,the timing of the application can vary. For example, in one embodiment,treatment with the stable topical ascorbic acid composition describedherein will commence at the beginning of the pregnancy, acting as apreventative treatment to the appearance and onset of striae. Incontrast, in other embodiments, the treatment may begin in the middle ofthe pregnancy term, at the end of the pregnancy term, or after thepregnancy term—when striae gravidarum have already appeared—in order todiminish and/or eliminate the size of the skin legions. Notably, none ofthese factors (i.e., frequency, duration, timing and type ofapplication) should be viewed as determinative or limiting to thedisclosed treatment modality.

In addition to use for the treatment of striae gravidarum in pregnantwomen, it is also contemplated that the disclosed stable topicalascorbic acid composition will be used for the treatment of pubertalstriae in adolescent individuals, individuals with Cushing's disease,steroid users, and other groups known now, or in the future, to besusceptible to the appearance of striae gravidarum. Again, thefrequency, duration, timing, and the type of application of the stableascorbic acid composition described herein to these groups is notdeterminative or limiting, as any application method known to those ofskill in the art is contemplated in these target groups. Further, itshould be noted that it is contemplated that the stable topical ascorbicacid composition disclosed herein can be utilized alone, or incombination with other treatments known now or in the future for thetreatment and/or prevention of striae gravidarum.

The hypothesized ability of a stabilized formulation of ascorbic acid,if properly formulated, to have a pharmacologic effect on the dermalfibroblasts, augmenting the production of normal collagen and elastin ofsufficient quantity and quality to stimulate collagen synthesis, hasapplication in other skin conditions or diseases associated with adisruption in collagen hydroxylation. One such condition is radiationdermatitis. In one embodiment of the disclosed method for treatment ofradiation dermatitis with the stable topical ascorbic acid compositiondisclosed herein, the composition is applied, via any method known tothose of skill in the art for application of a topical formulation, tothe skin of an individual undergoing radiation treatment prior to theindividual's first treatment. Any radiation treatment associated withthe onset of radiation dermatitis, now or in the future, is contemplatedas a treatment population for the disclosed topical ascorbic acidcomposition. In another embodiment of the disclosed method for treatmentof radiation dermatitis with the stable topical ascorbic acidcomposition disclosed herein, the stable topical ascorbic acidcomposition is applied during radiation treatment, preferably at theonset or within one to four weeks of treatment when early radiation skinreactions generally begin to occur. In still other embodiments, thetopical ascorbic acid composition described herein will be applied afterthe appearance of radiation skin reactions.

Akin to the methods for treating striae gravidarum with the topicalascorbic acid composition, the frequency, duration, timing and type ofapplication of the stable ascorbic acid composition described herein arenot determinative or limiting, as any frequency, duration, timing ortype of application known now, or in the future, to those of skill inthe art is contemplated. Further, it is contemplated that the topicalascorbic acid composition described herein may be used alone, or incombination with other treatments known to those of skill in the art forthe treatment and/or prevention of radiation dermatitis, such as, butnot limited to: washing, aloe vera, biafins (e.g., trolamine),hyaluronic acid cream, corticosteroids, sucralfate, barrier films,antimicrobials, dressings, and hydrophilic dressings.

In addition to use in methods for the treatment/prevention of striaegravidarum and radiation dermatitis, it is also contemplated that thestable topical ascorbic acid composition disclosed herein may beutilized in a method for the treatment and/or prevention of any otherskin disease or affliction associated with the break-down, degeneration,or disturbance of the collagen framework in human or other animal skin.Such skin conditions include, but are not limited to, rhytids (skinwrinkles), lentigoes, dyschromia, sun-damaged induced hyperpigmentation,cellulite, scars and sun induced or actinic pupura. Again, thefrequency, duration, timing and type of application of the stableascorbic acid composition described herein in these methods are notdeterminative or limiting. Further, the stable ascorbic acid solution ofthis disclosure can be used alone or in combination with othertreatments for the treatment and/or prevention of these diseases orconditions.

While the invention has been disclosed in connection with certainpreferred embodiments, this should not be taken as a limitation to allof the provided details. Modifications and variations of the describedembodiments may be made without departing from the spirit and scope ofthe invention, and other embodiments should be understood to beencompassed in the present disclosure as would be understood by those ofordinary skill in the art.

1. A method of stimulating collagen synthesis comprising: forming acomposition of ascorbic acid in solution with a hygroscopic compound;and applying said composition topically to a patient's skin.
 2. Themethod of claim 1, wherein the composition is topically applied to thepatient for the treatment of striae gravidarum.
 3. The method of claim1, wherein the composition is topically applied to the patient for thetreatment of radiation dermatitis.
 4. The method of claim 1, wherein thecomposition is topically applied to the patient for the treatment ofrhytids.
 5. The method of claim 1, wherein the composition is topicallyapplied to the patient for the treatment of lentigoes.
 6. The method ofclaim 1, wherein the composition is topically applied to the patient forthe treatment of dyschromia.
 7. The method of claim 1, wherein thecomposition is topically applied to the patient for the treatment ofsun-damage induced hyperpigmentation.
 8. The method of claim 1, whereinthe composition is topically applied to the patient for the treatment ofcellulite.
 9. The method of claim 1, wherein the composition istopically applied to the patient for the treatment of scars.
 10. Themethod of claim 1, wherein the composition is topically applied to thepatient for the treatment of pupura.